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U M?nning G K?nig R B Banati H Mechler C Czech J Gehrmann U Schreiter-Gasser C L Masters K Beyreuther 《The Journal of biological chemistry》1992,267(33):23950-23956
The mechanism of proteolytic breakdown of the beta A4-amyloid protein precursor (APP) has attracted much attention because of its relevance for Alzheimer's disease. Apart from the pathological role of APP in the amyloidogenesis, many efforts have been made to identify the functional significance of this widely expressed protein in various biological processes. Employing biochemical techniques, we demonstrate that APP is involved in the initiation of the immune response. Upon stimulation, it is expressed by the major functional types of T-lymphocytes, i.e. CD4+ and CD8+ cells. As was demonstrated for the CD4+ lymphoid cell line H9, APP is predominantly secreted. The remaining COOH-terminal fragments generated upon secretion were highly unstable. Of the APP produced by immunocompetent cells, considerable amounts were shown to be leukocyte-derived APP (L-APP). In addition, we were able to identify the KPI-containing L-APP isoform, L-APP733, as the major expressed L-APP isoform in immunocompetent cells, including rat microglial cells and astrocytes. The L-APP expression pattern of these cells showed high similarity. These findings seem to be indicative of an important function of APP within the immune system. Therefore, APP may be involved in various immunopathogenic conditions of the periphery and in the central nervous system. 相似文献
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Muscarinic regulation of phosphatidylinositol turnover and cyclic nucleotide metabolism in the heart 总被引:2,自引:0,他引:2
Stimulation of cardiac muscarinic receptors leads to increases in the synthesis and hydrolysis of the membrane phospholipid phosphatidylinositol (PI). Carbachol stimulates PI hydrolysis in right and left murine atria as well as in murine ventricule and dissociated embryonic chick heart cells. Muscarinic stimulation of PI hydrolysis is markedly attenuated in calcium-free medium, is not antagonized by isoproterenol, occurs after a latency of several minutes, and is half-maximally activated by approximately 10 microM carbachol. In contrast, muscarinic inhibition of cyclic AMP accumulation in the same preparations is calcium independent, is opposed by the effect of isoproterenol, is maximal in minutes, and is half-maximally activated by 0.1 microM carbachol. These differences demonstrate that the two muscarinic receptor-mediated events are probably unrelated and independent responses. The concentration of carbachol that causes half-maximal activation of PI hydrolysis is almost identical to that causing half muscarinic receptor occupancy as assessed by 3H-labeled (-)-quinuclidinyl benzilate binding. Thus activation of the PI response by carbachol appears to be closely linked to receptor occupancy, whereas cyclase inhibition may occur when only a small percentage of receptors are occupied. The possible role of the PI response in generating intracellular signals such as arachidonic acid release, cyclic GMP synthesis, or C-kinase activation is discussed. 相似文献
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Microsomal TPNH-cytochrome c reductase 总被引:1,自引:0,他引:1
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Primary malignant tumors of the hand 总被引:1,自引:0,他引:1
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The binding of aldolase to the particulate fraction of rat brain homogenate has been investigated. In addition to a degree of adsorption which was shown to be dependent upon ionic strength, pH, and the levels of a number of function dependent metabolites such as FDP and inorganic phosphate, a differential behavior of the individual isoenzymes of the AC series was observed in this tissue. Aldolase A4 was the most firmly bound isoenzyme, and the degree of association of the other isoenzymes decreased with increasing C-subunit content. These different adsorption properties of aldolase A and C have been discussed in relation to the general nature of the interaction between aldolase and the structural components of brain and the differential influence of this binding on the activity of the individual isoenzymes. 相似文献